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Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis.
Cancer Res 2015; 75(14):2949-60CR

Abstract

Dysregulation of androgen signaling and pericellular proteolysis is necessary for prostate cancer progression, but the links between them are still obscure. In this study, we show how the membrane-anchored serine protease TMPRSS2 stimulates a proteolytic cascade that mediates androgen-induced prostate cancer cell invasion, tumor growth, and metastasis. We found that matriptase serves as a substrate for TMPRSS2 in mediating this proinvasive action of androgens in prostate cancer. Further, we determined that higher levels of TMPRSS2 expression correlate with higher levels of matriptase activation in prostate cancer tissues. Lastly, we found that the ability of TMPRSS2 to promote prostate cancer tumor growth and metastasis was associated with increased matriptase activation and enhanced degradation of extracellular matrix nidogen-1 and laminin β1 in tumor xenografts. In summary, our results establish that TMPRSS2 promotes the growth, invasion, and metastasis of prostate cancer cells via matriptase activation and extracellular matrix disruption, with implications to target these two proteases as a strategy to treat prostate cancer.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan. Bureau of Investigation, Ministry of Justice, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.Department and Graduate Institute of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan. mslee2006@ntu.edu.tw.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26018085

Citation

Ko, Chun-Jung, et al. "Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis." Cancer Research, vol. 75, no. 14, 2015, pp. 2949-60.
Ko CJ, Huang CC, Lin HY, et al. Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis. Cancer Res. 2015;75(14):2949-60.
Ko, C. J., Huang, C. C., Lin, H. Y., Juan, C. P., Lan, S. W., Shyu, H. Y., ... Lee, M. S. (2015). Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis. Cancer Research, 75(14), pp. 2949-60. doi:10.1158/0008-5472.CAN-14-3297.
Ko CJ, et al. Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis. Cancer Res. 2015 Jul 15;75(14):2949-60. PubMed PMID: 26018085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis. AU - Ko,Chun-Jung, AU - Huang,Cheng-Chung, AU - Lin,Hsin-Ying, AU - Juan,Chun-Pai, AU - Lan,Shao-Wei, AU - Shyu,Hsin-Yi, AU - Wu,Shang-Ru, AU - Hsiao,Pei-Wen, AU - Huang,Hsiang-Po, AU - Shun,Chia-Tung, AU - Lee,Ming-Shyue, Y1 - 2015/05/27/ PY - 2014/11/07/received PY - 2015/04/15/accepted PY - 2015/5/29/entrez PY - 2015/5/29/pubmed PY - 2015/10/7/medline SP - 2949 EP - 60 JF - Cancer research JO - Cancer Res. VL - 75 IS - 14 N2 - Dysregulation of androgen signaling and pericellular proteolysis is necessary for prostate cancer progression, but the links between them are still obscure. In this study, we show how the membrane-anchored serine protease TMPRSS2 stimulates a proteolytic cascade that mediates androgen-induced prostate cancer cell invasion, tumor growth, and metastasis. We found that matriptase serves as a substrate for TMPRSS2 in mediating this proinvasive action of androgens in prostate cancer. Further, we determined that higher levels of TMPRSS2 expression correlate with higher levels of matriptase activation in prostate cancer tissues. Lastly, we found that the ability of TMPRSS2 to promote prostate cancer tumor growth and metastasis was associated with increased matriptase activation and enhanced degradation of extracellular matrix nidogen-1 and laminin β1 in tumor xenografts. In summary, our results establish that TMPRSS2 promotes the growth, invasion, and metastasis of prostate cancer cells via matriptase activation and extracellular matrix disruption, with implications to target these two proteases as a strategy to treat prostate cancer. SN - 1538-7445 UR - https://www.unboundmedicine.com/medline/citation/26018085/Androgen_Induced_TMPRSS2_Activates_Matriptase_and_Promotes_Extracellular_Matrix_Degradation_Prostate_Cancer_Cell_Invasion_Tumor_Growth_and_Metastasis_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=26018085 DB - PRIME DP - Unbound Medicine ER -